tbuckley/cabot-search huggingface dataset:
Abstract P301: Diet Quality and Frailty in Israeli Adults 65 Years or Older
Authors: Abigail Goshen, Uri Goldbourt, Yael Benyamini, Tal Shimony, Lital Keinan Boker, Yariv Gerber
Journal: Circulation (2023)

Background: Frailty represents a transition state between successful aging and disability. Nutrition may promote successful aging. However, only a few studies explicitly examined the association between overall diet quality and frailty in the oldest old age group. Methods: We studied an older adult (65+) cohort that participated in the Israeli National Health and Nutrition Survey of Older Adults in 2005-2006 (T1, N=1,799). Survivors of T1 were contacted, and from 2017-2019, an extensive interview and a functional assessment were conducted (T2) among 604 past participants. A 24-hour dietary recall, assessed at T1, was used to calculate the healthy eating index (HEI-2015), a measure of diet quality used to assess how well a set of foods aligns with key recommendations. A frailty index (FI) based on accumulation of deficits was developed and comprised 33 variables, including clinical, functional, and cognitive measures. A threshold of ≥ 0.26 was used to define frailty. Frail participants at T1 were excluded from the analysis (n=125). Logistic regression models were constructed to assess the association of HEI-2015 with frailty incidence. Inverse probability weighting was used to minimize attrition bias. Results: Among the 479 T2 participants analyzed (mean [SD], age 84 [5] years, 50% women), 225 (46%) were classified as frail. Frail participants were older, less educated, with a lower household income and a higher comorbidity burden at baseline than non-frail subjects. After adjustment for sociodemographic and lifestyle factors, a higher HEI-2015 score was associated with decreased odds of incident frailty [odds ratio, 0.56 (95% CI: (0.35-0.90), for the upper tertile; 0.68, (95% CI: 0.42-1.09), for the middle tertile, compared with the lower tertile ( P for trend = .005). A spline analysis supported a linear decline in frailty with increasing HEI-2015 scores (Figure). Conclusion: In this cohort study of oldest-old participants, improved diet quality was inversely associated with frailty incidence in a dose-dependent manner.
Abstract 09: Trajectories of Insulin Resistance, Incident Heart Failure and All-Cause Death in Nondiabetics: The Atherosclerosis Risk in Communities Study
Authors: Zailing Xing, Douglas D Schocken, Janice Zgibor, Amy C Alman
Journal: Circulation (2023)

Introduction: Previous studies have suggested an association between insulin resistance (IR) trajectories and adverse changes in cardiac structure and function in nondiabetic populations. We studied the associations between IR trajectories and incident heart failure (HF) and all-cause death in nondiabetic participants of the Atherosclerosis Risk in Communities (ARIC) study. We hypothesized that long-term moderate and high IR levels would increase the risk of incident HF and all-cause death. Methods: We included 7,835 participants (3,505 men and 4,330 women) aged 45-64 from the ARIC study without diabetes mellitus at any visit, and no history of prevalent HF, myocardial infarction, stroke, arterial or coronary surgery, or cancer at baseline. We estimated IR using Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride glucose (TyG) index and metabolic score for IR (METS-IR). Serum insulin was not available at visits 2 and 3, so HOMA-IR was calculated for visits 1, 4, and 5. Latent class analysis identified two HOMA-IR trajectories, low-increasing and high-increasing, and three trajectories for TG/HDL-C, TyG index, and METS-IR: low-increasing, moderate-stable, and high-decreasing. We employed Cox proportional-hazards models to examine the associations of IR trajectories with incident HF and all-cause death adjusting for potential confounders. Results: Compared to participants in the low-increasing group, those in the high-increasing group of HOMA-IR were more likely to have incident HF and all-cause death (Table 1). For TG/HDL-C, TyG index and METS-IR, we found an increased risk of incident HF in the moderate-stable and high-decreasing groups relative to the low-increasing group. For all-cause death, consistent associations were found only in women (Table 1). Conclusions: Reduction of insulin resistance in nondiabetic individuals may be a suitable target for prevention strategies to reduce cardiovascular disease.
Abstract P274: Associations of Occupational Physical Activity With Allostatic Load Among Workers in the United States
Authors: Tong Xia, Jian Li, Liwei Chen
Journal: Circulation (2023)

Introduction: Occupational physical activity (OPA) has been linked to adverse cardiovascular outcomes and mortality among workers, but underlying mechanisms are not clear. Allostatic load (AL) presents a measure of the accumulative burden of chronic stress and may play a role in the association of OPA with cardiovascular outcomes. We hypothesized that OPA was positively associated with AL in workers. Methods: Analyses were conducted in 6487 United States (U.S.) workers (i.e., working at a job or business) aged 20-60 years who were not pregnant, had data on moderate-to-vigorous OPA and biomarkers for AL calculation using a national representative sample, the National Health and Nutrition Examination Survey (2007-2018). OPA was dichotomized primarily by time spent on moderate-to-vigorous OPA (i.e., high: ≥ 150 vs. low: &lt; 150; min/week) and secondarily by energy spent on it (i.e., high: ≥ median vs. low: &lt; median; kcal/week). AL score was calculated using a common method from 9 biomarkers with a range of 0-9. Associations of OPA with AL were assessed using multivariable linear regression models with sampling weights applied to represent U.S. workers. Results: AL score was significantly higher among workers who spent higher time on moderate-to-vigorous OPA (β = 0.11, P = 0.02) or had higher energy on it (β = 0.10, P = 0.05) than their counterparts. When stratified by gender and age, the positive associations of OPA with AL remained significant only among females aged 20-40 years (β = 0.16, P = 0.02 for higher time on moderate-to-vigorous OPA; β = 0.35, P &lt; 0.001 for higher energy on moderate-to-vigorous OPA), but such associations were not observed in other groups (females aged 41-60 years, males aged 20-40 years, and males aged 41-60 years). Conclusions: We found that OPA was positively associated with AL among U.S. workers, particularly in young female workers. Our findings are novel and worthy of further studies to confirm the role of OPA in explaining cardiometabolic disorders.
Abstract P472: Matching Young Adult Strokes in a Claims Database to the Clinical Get With the Guidelines-Stroke Registry
Authors: Michelle H Leppert, Sharon N Poisson, Sharon Scarbro, Remy Poudel, Quiera Booker, Krithika Suresh, Lynda D Lisabeth, Lee H Schwamm, Stacie L Daugherty, Cathy Bradley, James F Burke, Michael Ho
Journal: Circulation (2023)

Background: Due to its lower incidence, strokes in young adults, studies have difficulty answering why there are more women than men less than 35 with incident strokes. The goal of this study is to link claims and registry data to create a new longitudinal and clinical cohort of strokes in young adults. Methods: Colorado mandates reporting of commercial and public insurance (Medicaid and Medicare) claims to the All Payer Claims Database (APCD). We identified all first-time stroke admissions using ICD-9 /10 codes between 2012 to 2018 in young adults (18-55). Get with the Guidelines (GWTG) Stroke registry has stroke cases from 41 hospitals in Colorado since 2010. Matching was based on exact birthdate, sex and +/- 1day in admission/discharge dates. Confirmation of match was based on comparing the admitting hospital between the two databases. Cardiovascular(CV) and non-CV risk factors occurring from enrollment until 1 day prior to stroke date in the APCD were included. Student’s T-test, and Z-tests were used to test differences between men and women. Results: We identified 3032 stroke cases in the APCD. Of these, 1455 (48.0%) matched to an admission in the GWTG-Stroke registry. Of these, 1303 (89.6%) also matched based on the admitting hospital (Table). The final cohort contained 51% women, 11.3% &lt;35, 35.2% between 35-45, and 63.5% between 45-55. The most common CV risk factors were hypertension, hyperlipidemia, and tobacco use in men, and hypertension, tobacco use, and obesity in women. The most common non-CV risk factors were migraines, renal failure, thrombophilia in men and migraines, malignancy, and thrombophilia in women. The prevalence of cardiovascular risk factors was higher in men, while the prevalence of non-cardiovascular risk factors was higher in women. There was no difference in the severity of strokes between men and women. Conclusions: Clinical registries such as GWTG-Stroke can be used to supplement longitudinal administrative cohorts of young adults with stroke to get richer data on stroke etiology and severity.
Abstract P602: Complete Blood Count Analysis in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study With a Point of Care Instrument
Authors: Margaret King, April Perry, Elaine S Cornell, Rebekah Boyle, Suzanne E Judd, James D Rhodes, Vasan S Ramachandran, Russell Tracy, Jon P Durda
Journal: Circulation (2023)

Background: The RURAL cohort study is a uniquely designed study using a Mobile Examination Unit (MEU) to study heart and lung disorders in rural counties in the southeastern US. Complete blood counts (CBC) are included in the participant baseline examination. We wanted to use an instrument in the MEU for onsite blood counts and chose the Pixcell Hemoscreen, a point-of-care instrument using a unique technology. Before using the Hemoscreen in the RURAL study, it was necessary to ensure that the CBC results would be comparable to laboratory generated results. Methods: We compared CBC results from the Hemoscreen to those from the Sysmex XN9000 at the University of Vermont Medical Center. CBC measurements include erythrocyte count (RBC), white blood cell count (WBC), hemoglobin concentration (HGB), hematocrit value (HCT), and platelet count (PLT). Blood from ten volunteers was analyzed on the Hemoscreen and the Sysmex. Statistics included average, standard deviation, and coefficient of variance (CV) for each of the parameters analyzed. Blood from ten volunteers was assayed on both the Hemoscreen and the Sysmex to compare for accuracy. Blood from three volunteers was analyzed ten times on the Hemoscreen to assess variability. Results: The Hemoscreen and Sysmex reported similar values for WBC, RBC, HCT, HGB and PLT counts, as shown in Figure 1. Between repeat measures conducted on the same sample on the Hemoscreen WBC, RBC, HCT, HGB and PLT showed little variance (%CV = 5.9, 2.7, 2.8, 2.7, and 4.0 respectively). Conclusions: The Hemoscreen data correlated with data generated in a hospital laboratory on the same samples. Variability between multiple measures of the same samples on the Hemoscreen showed acceptable variance. To date over 730 RURAL participants have been seen and the Hemoscreen has proven to be quick, accurate, and reliable.
Abstract P162: Sex Differences in Cardiometabolic Biomarkers During Pre-Diabetes
Authors: Yilin Yoshida, Zhipeng Chen, Changwei Li, Franck Mauvais-Jarvis
Journal: Circulation (2023)

Background: Diabetes (DM) diminishes female protection against cardiovascular disease (CVD). Women with DM face excess CVD risk than men partly due to women’s greater deterioration in risk factors before DM. In this study, we compared sex differences in biomarkers that reflect distinct pathophysiological pathways during the pre-diabetes (pre-DM) stage. Method: A cross-sectional analysis was performed based on pooled data from Atherosclerosis Risk in Communities Study and the Jackson Heart Study. We used multivariable linear regressions to examine the associations between sex and biomarkers (log-transformed) representative of inflammation, lipoprotein, adipokine, kidney function, cardiac injury/stress, and thrombosis, adjusted for age, race, and BMI, among CVD-free individuals with pre-DM. We validated the results in a sensitivity analysis, including those that eventually progressed into DM during the follow-up. We used the false discovery rate method to adjust multiple comparisons. Results: Among 5975 individuals with pre-DM, the mean age was 54.2 years, 2853 (48%) were women, and 2022 (34%) were non-Hispanic blacks. In the adjusted models, inflammatory biomarkers, including high-sensitivity c-reactive proteins (β coefficient 0.2, P=2.9 x 10 -9 ), fibrinogen (β 0.19, P=2.8E-12), and absolute lymphocyte (β 0.25, P=2.54 x 10 -7 ), and cardiac injury/stress biomarker, NT-proBNT (β 0.14, P=0.0002) were higher in women than men with pre-DM. Additionally, lipoprotein(a) (β 0.19, P=4.96 x 10 -13 ) and apolipoproteins A1 (β 0.61, P=2.81x 10 -120 ), and adipokines including leptin (β 1.1, P=2.62 x 10 -123 ) and adiponectin (β 0.56, P=1.94 x 10 -12 ) were all higher in women with pre-DM. In contrast, kidney function markers, albumin (β -0.24, P=2.79 x 10 -9 ) and creatinine (β -1.1, P=1x 10 -100 ), and thrombosis biomarker, homocysteine (β -0.5, P=9.09 x 10 -19 ) were higher in men with pre-DM than in their women counterparts. These sex differences remained generally unchanged among 2320 individuals that progressed into DM. Conclusion: Biomarkers differ significantly between sexes during the pre-DM state. The inflammatory, lipoprotein, adipokine, and cardiac stress biomarkers were higher in women with pre-DM, while kidney function and thrombosis biomarkers were higher in men with pre-DM. Future mechanistic studies are warranted to delineate pathophysiological pathways characterized by these biomarkers contributing to sex disparities of CVD risk in DM.
Abstract P193: Sexual Minority Men of Color With HIV Suggest a Virtual Environment May Be Promising to Support Cardiovascular Health: Findings From an Intervention Mapping Study
Authors: S. Raquel Ramos, Maame-Owusua Boateng, Lauren Chin, Jon Andre Sabio Parrilla
Journal: Circulation (2023)

Introduction: Black and Latinx sexual minority men are disproportionately impacted by chronic conditions, such as HIV. Persons with HIV have a 1.5 to 2 times risk of cardiovascular disease (CVD) when compared to White, HIV-negative persons. By the year 2030, it is estimated that 78% of persons with HIV will have CVD. Patient teaching in the clinical setting has been the traditional modality for prevention education. However, persons at the highest risk, and who are based in the community, may not have access to clinic-based prevention education. Objective: To use mixed methods to assess HIV illness perceptions, HIV-related comorbid conditions of concern, and understand perspectives on the use of an online virtual environment (VE) for CVD prevention education. Methods: The Gaming Protocol Study is a mixed methods study that used Life’s Simple 7 as a framework to map an intervention to support cardiovascular health in sexual minority men of color with HIV, ages 30-65. Data were collected in English, Spanish, and Creole. Using validated measures, HIV illness perceptions, nicotine exposure, and physical activity were assessed. Qualitative interviews explored chronic illnesses of concern outside of HIV and also perceptions about the use of an online VE for CVD prevention education. Results: Thirty participants completed the validated measures and interviews. Quantitative findings suggested that greater than 90% of participants had a strong understanding of their HIV status. More than 50% of participants reported they experienced feelings of anxiety or fear by having HIV. Close to 30% reported having used nicotine and/or e-cigarettes. Less than half of participants met the criteria for engaging in vigorous or moderate physical activity. Qualitative findings suggested concerns about existing and potential future conditions, such as hypertension, diabetes, asthma, obesity, and mental health. Additionally, COVID-19 and Monkeypox were highlighted as important considerations because they pose high risk in the community. Perceptions about using a VE were mostly positive. Concerns were focused on online engagement and digital privacy. Conclusions: Sexual minority men of color are concerned about health conditions beyond HIV. They desire accessible, culturally relevant information to manage their health. Findings provide early evidence about health communication and education preferences for technology tools so they are meaningful and actionable as CVD prevention education.
Abstract P153: Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus Results in a More Favorable Sex Hormone Profile in Both Post-Menopausal Females and Older Males (The Look AHEAD Trial Sex Hormone Study)
Authors: Vidya Chandran, Wendy Bennett, Erin D Michos, Rita R Kalyani, Jeanne Clark, Mark Woodward, Jiajun Wu, Allen D Everett, Jun Yang, Jie Zhu, David Graham, Susan Aja, Greg Ellis, Dhananjay Vaidya
Journal: Circulation (2023)

Background: Prior studies showed an association between some adverse cardiometabolic outcomes and lower testosterone in males and higher estrogen in both males and post-menopausal females. However, few studies of sex hormones focused on people with type 2 diabetes (T2DM), assessed hormone changes over time or applied highly sensitive laboratory assays. Given the importance of lifestyle modification (i.e., diet, exercise and weight loss) in preventing cardiometabolic complications in people with T2DM, we examined the impact of an Intensive Lifestyle Intervention (ILI) on sex hormones over time and differences by sex. Methods: The Look AHEAD (Action for Health in Diabetes) Study was a randomized control trial of 5,145 individuals with BMI ≥25 and T2D to evaluate the effect of ILI compared to the Diabetes Support and Education (DSE) control group on incident cardiovascular events. We selected a sample of 472 males and 426 post-menopausal female participants (mean age 60 years [SD 6.3], 20.5% Black) to examine sex hormones (estradiol - E2, total testosterone - T) and sex hormone binding globulin (SHBG) at baseline and year 1. E2 and T were measured using mass spectrometry analysis and SHBG was measured using an immunoassay. Results: In males, ILI increased SHBG by 17.3% and T by 10.6% compared to the DSE group (Table). In postmenopausal females, ILI increased SHBG by 12.0% and decreased E2 by 23.4% compared to the DSE group (Table). The change in the sex hormone levels from baseline to 1-year follow up was attenuated when adjusted for change in BMI. Conclusion: ILI resulting in weight loss increased T in males and decreased E2 in postmenopausal females and increased SHBG in both sexes. We plan further analysis with a larger sample and longer follow-up to examine the role of weight loss either as a co-occurring metabolic process or as a mediator for the change in sex hormones to better understand the impact of lifestyle changes and sex diffrences.
Combinatorial batching of DNA for ultralow-cost detection of pathogenic variants
Authors: Ulrik Kristoffer Stoltze, Christian Munch Hagen, Thomas van Overeem Hansen, Anna Byrjalsen, Anne-Marie Gerdes, Victor Yakimov, Simon Rasmussen, Marie Bækvad-Hansen, David Michael Hougaard, Kjeld Schmiegelow, Henrik Hjalgrim, Karin Wadt, Jonas Bybjerg-Grauholm
Journal: Genome Medicine (2023)

Abstract Background Next-generation sequencing (NGS) based population screening holds great promise for disease prevention and earlier diagnosis, but the costs associated with screening millions of humans remain prohibitive. New methods for population genetic testing that lower the costs of NGS without compromising diagnostic power are needed. Methods We developed double batched sequencing where DNA samples are batch-sequenced twice — directly pinpointing individuals with rare variants. We sequenced batches of at-birth blood spot DNA using a commercial 113-gene panel in an explorative ( n = 100) and a validation ( n = 100) cohort of children who went on to develop pediatric cancers. All results were benchmarked against individual whole genome sequencing data. Results We demonstrated fully replicable detection of cancer-causing germline variants, with positive and negative predictive values of 100% (95% CI, 0.91–1.00 and 95% CI, 0.98–1.00, respectively). Pathogenic and clinically actionable variants were detected in RB1 , TP53 , BRCA2 , APC , and 19 other genes. Analyses of larger batches indicated that our approach is highly scalable, yielding more than 95% cost reduction or less than 3 cents per gene screened for rare disease-causing mutations. We also show that double batched sequencing could cost-effectively prevent childhood cancer deaths through broad genomic testing. Conclusions Our ultracheap genetic diagnostic method, which uses existing sequencing hardware and standard newborn blood spots, should readily open up opportunities for population-wide risk stratification using genetic screening across many fields of clinical genetics and genomics.
Cell-specific clock-controlled gene expression program regulates rhythmic fiber cell growth in cotton
Authors: Dehe Wang, Xiao Hu, Hanzhe Ye, Yue Wang, Qian Yang, Xiaodong Liang, Zilin Wang, Yifan Zhou, Miaomiao Wen, Xueyan Yuan, Xiaomin Zheng, Wen Ye, Boyu Guo, Mayila Yusuyin, Eugenia Russinova, Yu Zhou, Kun Wang
Journal: Genome biology (2023)

Abstract Background The epidermis of cotton ovule produces fibers, the most important natural cellulose source for the global textile industry. However, the molecular mechanism of fiber cell growth is still poorly understood. Results Here, we develop an optimized protoplasting method, and integrate single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to systematically characterize the cells of the outer integument of ovules from wild type and fuzzless/lintless ( fl ) cotton (Gossypium hirsutum ). By jointly analyzing the scRNA-seq data from wildtype and fl, we identify five cell populations including the fiber cell type and construct the development trajectory for fiber lineage cells. Interestingly, by time-course diurnal transcriptomic analysis, we demonstrate that the primary growth of fiber cells is a highly regulated circadian rhythmic process. Moreover, we identify a small peptide GhRALF1 that circadian rhythmically controls fiber growth possibly through oscillating auxin signaling and proton pump activity in the plasma membrane. Combining with scATAC-seq, we further identify two cardinal cis-regulatory elements (CREs, TCP motif, and TCP-like motif) which are bound by the trans factors GhTCP14s to modulate the circadian rhythmic metabolism of mitochondria and protein translation through regulating approximately one third of genes that are highly expressed in fiber cells. Conclusions We uncover a fiber-specific circadian clock-controlled gene expression program in regulating fiber growth. This study unprecedentedly reveals a new route to improve fiber traits by engineering the circadian clock of fiber cells.